Host defense peptide ‐derived privileged scaffolds for anti‐infective drug discovery

We report here that in addition to the previously reported antibacterial activity on planktonic bacteria, the γ‐core peptide is active against biofilm formation and maturation. We also show that it is readily cell penetrant, like HBD3, although with a different mechanism, which is independent from CD98. Overall, the potency of the single‐disulfide, 23‐amino acid γ‐core is comparable with the full‐length peptide across the whole spectrum of examined properties, and the peptide is not toxic to human cells. The HBD3 γ‐core peptide may therefore represent the first example of an economically viable lead peptide derived from a HDP privileged scaffold. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd. Peptide privileged scaffolds with a multiple‐disulfide framework display a broad range of biological effects, but with challenging synthesis and high manufacturing cost. Simplified privileged scaffolds are found in the common structural signature of host defense peptides (HDPs), named the γ‐core. The single‐disulfide, 23‐amino acid γ‐core of human β‐defensin‐3 is stable in human serum and displays many of the biological activities of the full‐length peptide, representing an economically viable lead peptide derived from a HDP privileged scaffold.
Source: Journal of Peptide Science - Category: Biochemistry Authors: Tags: Special Issue Article Source Type: research